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Viruses, Volume 12, Issue 11 (November 2020) – 142 articles

Cover Story (view full-size image): HIV-1 cure strategy by means of proviral knock-out using CRISPR-Cas9 has been hampered by the emergence of viral resistance against the targeting guide RNA (gRNA). Rapid viral rebound was evident after Cas9-gRNA disruption, due to the non-homologous end-joining (NHEJ)-mediated mutations inside the targeted proviral regions (e.g., LTR) that are non-deleterious to the virus. Here, we propose concentrated gRNA attacks against the integral HIV-1 tat to deplete post-editing viral fitness and block mutational escape. Analogous to the combination strategy of antiretroviral therapy (ART), combination of multiple gRNAs represents a promising method to inhibit viral escape from CRISPR-Cas9, thus elevating the gene editing platform to achieve long-term HIV-1 cure. View this paper.
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Open AccessArticle
Global Occurrence of Clinically Relevant Hepatitis B Virus Variants as Found by Analysis of Publicly Available Sequencing Data
Viruses 2020, 12(11), 1344; https://doi.org/10.3390/v12111344 - 23 Nov 2020
Viewed by 313
Abstract
Several viral factors impact the natural course of hepatitis B virus (HBV) infection, the sensitivity of diagnostic tests, or treatment response to interferon-α and nucleos(t)ide analogues. These factors include the viral genotype and serotype but also mutations affecting the HBV surface antigen, basal [...] Read more.
Several viral factors impact the natural course of hepatitis B virus (HBV) infection, the sensitivity of diagnostic tests, or treatment response to interferon-α and nucleos(t)ide analogues. These factors include the viral genotype and serotype but also mutations affecting the HBV surface antigen, basal core promoter/pre-core region, or reverse transcriptase. However, a comprehensive overview of the distribution of HBV variants between HBV genotypes or different geographical locations is lacking. To address this, we performed an in silico analysis of publicly available HBV full-length genome sequences. We found that not only the serotype frequency but also the majority of clinically relevant mutations are primarily associated with specific genotypes. Distinct mutations enriched in certain world regions are not explained by the local genotype distribution. Two HBV variants previously identified to confer resistance to the nucleotide analogue tenofovir in vitro were not identified, questioning their translational relevance. In summary, our work elucidates the differences in the clinical manifestation of HBV infection observed between genotypes and geographical locations and furthermore helps identify suitable diagnostic tests and therapies. Full article
(This article belongs to the Special Issue Hepatitis B Virus: From Diagnostics to Treatments)
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Open AccessArticle
High-Throughput Method for Detection of Arbovirus Infection of Saliva in Mosquitoes Aedes aegypti and Ae. albopictus
Viruses 2020, 12(11), 1343; https://doi.org/10.3390/v12111343 - 23 Nov 2020
Viewed by 422
Abstract
Vector competence refers to the ability of a vector to acquire, maintain, and transmit a pathogen. Collecting mosquito saliva in medium-filled capillary tubes has become the standard for approximating arbovirus transmission. However, this method is time-consuming and labor-intensive. Here we compare the capillary [...] Read more.
Vector competence refers to the ability of a vector to acquire, maintain, and transmit a pathogen. Collecting mosquito saliva in medium-filled capillary tubes has become the standard for approximating arbovirus transmission. However, this method is time-consuming and labor-intensive. Here we compare the capillary tube method to an alternative high-throughput detection method the collection of saliva on paper cards saturated with honey, with (FTA card) and without (filter paper) reagents for the preservation of nucleic acid for Aedes aegypti and Aedes albopictus mosquitoes infected with two emerging genotypes of the chikungunya virus (CHIKV). Model results showed that the Asian genotype CHIKV dissemination in the harvested legs of both Ae. aegypti and Ae. albopictus increased the odds of females having a positive salivary infection and higher salivary viral titers, while for the IOL genotype the same effect was observed only for Ae. aegypti. Of the three tested detection methods, the FTA card was significantly more effective at detecting infected saliva of Ae. aegypti and Ae. albopictus females than the capillary tube and filter paper was as effective as the capillary tube for the Asian genotype. We did not find significant effects of the detection method in detecting higher viral titer for both Asian and IOL genotypes. Our results are discussed in light of the limitations of the different tested detection methods. Full article
(This article belongs to the Special Issue Alphaviruses: Interactions between Arboviruses and Mosquitoes)
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Open AccessArticle
Examining the Association of Socioeconomic Position with Microcephaly and Delayed Childhood Neurodevelopment among Children with Prenatal Zika Virus Exposure
Viruses 2020, 12(11), 1342; https://doi.org/10.3390/v12111342 - 23 Nov 2020
Viewed by 349
Abstract
Increased rates of Zika virus have been identified in economically deprived areas in Brazil at the population level; yet, the implications of the interaction between socioeconomic position and prenatal Zika virus exposure on adverse neurodevelopmental outcomes remains insufficiently evaluated at the individual level. [...] Read more.
Increased rates of Zika virus have been identified in economically deprived areas in Brazil at the population level; yet, the implications of the interaction between socioeconomic position and prenatal Zika virus exposure on adverse neurodevelopmental outcomes remains insufficiently evaluated at the individual level. Using data collected between September 2015 and September 2019 from 163 children with qRT-PCR and/or IgM-confirmed prenatal exposure to Zika virus participating in a prospective cohort study in Rio de Janeiro, Brazil (NCT03255369), this study evaluated the relationships of socioeconomic indicators with microcephaly at birth and Bayley-III neurodevelopmental scores during the early life course. Adjusted logistic regression models indicated increased odds of microcephaly in children born to families with lower household income (OR, 95% CI: 3.85, 1.43 to 10.37) and higher household crowding (OR, 95% CI: 1.83, 1.16 to 2.91), while maternal secondary and higher education appeared to have a protective effect for microcephaly compared to primary education (OR, 95% CI: 0.33, 0.11 to 0.98 and 0.10, 0.03 to 0.36, respectively). Consistent with these findings, adjusted linear regression models indicated lower composite language (−10.78, 95% CI: −19.87 to −1.69), motor (−10.45, 95% CI: −19.22 to −1.69), and cognitive (−17.20, 95% CI: −26.13 to −8.28) scores in children whose families participated in the Bolsa Família social protection programme. As such, the results from this investigation further emphasise the detrimental effects of childhood disadvantage on human health and development by providing novel evidence on the link between individual level socioeconomic indicators and microcephaly and delayed early life neurodevelopment following prenatal Zika virus exposure. Full article
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Open AccessOpinion
A Perspective on Organoids for Virology Research
Viruses 2020, 12(11), 1341; https://doi.org/10.3390/v12111341 - 23 Nov 2020
Viewed by 282
Abstract
Animal models and cell lines are invaluable for virology research and host–pathogen interaction studies. However, it is increasingly evident that these models are not sufficient to fully understand human viral diseases. With the advent of three-dimensional organotypic cultures, it is now possible to [...] Read more.
Animal models and cell lines are invaluable for virology research and host–pathogen interaction studies. However, it is increasingly evident that these models are not sufficient to fully understand human viral diseases. With the advent of three-dimensional organotypic cultures, it is now possible to study viral infections in the human context. This perspective explores the potential of these organotypic cultures, also known as organoids, for virology research, antiviral testing, and shaping the virology landscape. Full article
(This article belongs to the Special Issue The Application of 3D Tissue Culture Systems in Virology)
Open AccessArticle
LysSAP26, a New Recombinant Phage Endolysin with a Broad Spectrum Antibacterial Activity
Viruses 2020, 12(11), 1340; https://doi.org/10.3390/v12111340 - 23 Nov 2020
Viewed by 269
Abstract
Multidrug-resistant (MDR) bacteria are a major threat to public health. Bacteriophage endolysins (lysins) are a promising alternative treatment to traditional antibiotics. However, the lysins currently under development are still underestimated. Herein, we cloned the lysin from the SAP-26 bacteriophage genome. The recombinant LysSAP26 [...] Read more.
Multidrug-resistant (MDR) bacteria are a major threat to public health. Bacteriophage endolysins (lysins) are a promising alternative treatment to traditional antibiotics. However, the lysins currently under development are still underestimated. Herein, we cloned the lysin from the SAP-26 bacteriophage genome. The recombinant LysSAP26 protein inhibited the growth of carbapenem-resistant Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, oxacillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium with minimum inhibitory concentrations of 5~80 µg/mL. In animal experiments, mice infected with A. baumannii were protected by LysSAP26, with a 40% survival rate. Transmission electron microscopy analysis confirmed that LysSAP26 treatment resulted in the destruction of bacterial cell walls. LysSAP26 is a new endolysin that can be applied to treat MDR A. baumannii, E. faecium, S. aureus, K. pneumoniae, P. aeruginosa, and E. coli infections, targeting both Gram-positive and Gram-negative bacteria. Full article
(This article belongs to the Section Bacterial Viruses)
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Open AccessEditorial
COVID-19 and School Activities in Italy
Viruses 2020, 12(11), 1339; https://doi.org/10.3390/v12111339 - 23 Nov 2020
Viewed by 294
Abstract
After a linear growth during September, the diffusion in Italy of SARS-CoV-2, responsible for COVID-19, has been growing exponentially since the end of that month with a doubling time approximately equal to one week [...] Full article
(This article belongs to the collection Coronaviruses)
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Open AccessReview
Plant Virology Delivers Diverse Toolsets for Biotechnology
Viruses 2020, 12(11), 1338; https://doi.org/10.3390/v12111338 - 23 Nov 2020
Viewed by 355
Abstract
Over a hundred years of research on plant viruses has led to a detailed understanding of viral replication, movement, and host–virus interactions. The functions of vast viral genes have also been annotated. With an increased understanding of plant viruses and plant–virus interactions, various [...] Read more.
Over a hundred years of research on plant viruses has led to a detailed understanding of viral replication, movement, and host–virus interactions. The functions of vast viral genes have also been annotated. With an increased understanding of plant viruses and plant–virus interactions, various viruses have been developed as vectors to modulate gene expressions for functional studies as well as for fulfilling the needs in biotechnology. These approaches are invaluable not only for molecular breeding and functional genomics studies related to pivotal agronomic traits, but also for the production of vaccines and health-promoting carotenoids. This review summarizes the latest progress in these forefronts as well as the available viral vectors for economically important crops and beyond. Full article
(This article belongs to the Special Issue The Application of Viruses to Biotechnology)
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Open AccessReview
Host Range and Coding Potential of Eukaryotic Giant Viruses
Viruses 2020, 12(11), 1337; https://doi.org/10.3390/v12111337 - 21 Nov 2020
Viewed by 672
Abstract
Giant viruses are a group of eukaryotic double-stranded DNA viruses with large virion and genome size that challenged the traditional view of virus. Newly isolated strains and sequenced genomes in the last two decades have substantially advanced our knowledge of their host diversity, [...] Read more.
Giant viruses are a group of eukaryotic double-stranded DNA viruses with large virion and genome size that challenged the traditional view of virus. Newly isolated strains and sequenced genomes in the last two decades have substantially advanced our knowledge of their host diversity, gene functions, and evolutionary history. Giant viruses are now known to infect hosts from all major supergroups in the eukaryotic tree of life, which predominantly comprises microbial organisms. The seven well-recognized viral clades (taxonomic families) have drastically different host range. Mimiviridae and Phycodnaviridae, both with notable intrafamilial genome variation and high abundance in environmental samples, have members that infect the most diverse eukaryotic lineages. Laboratory experiments and comparative genomics have shed light on the unprecedented functional potential of giant viruses, encoding proteins for genetic information flow, energy metabolism, synthesis of biomolecules, membrane transport, and sensing that allow for sophisticated control of intracellular conditions and cell-environment interactions. Evolutionary genomics can illuminate how current and past hosts shape viral gene repertoires, although it becomes more obscure with divergent sequences and deep phylogenies. Continued works to characterize giant viruses from marine and other environments will further contribute to our understanding of their host range, coding potential, and virus-host coevolution. Full article
(This article belongs to the collection Unconventional Viruses)
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Open AccessArticle
Diagnostic Performances of Different Genome Amplification Assays for the Detection of Swine Vesicular Disease Virus in Relation to Genomic Lineages That Circulated in Italy
Viruses 2020, 12(11), 1336; https://doi.org/10.3390/v12111336 - 20 Nov 2020
Viewed by 324
Abstract
During the last 25 years, swine vesicular disease (SVD) has occurred in Italy mostly sub-clinically. Therefore, regular testing of fecal samples from suspected holdings and high turnover premises was fundamental to identifying virus circulation and to achieve SVD eradication. In this study, we [...] Read more.
During the last 25 years, swine vesicular disease (SVD) has occurred in Italy mostly sub-clinically. Therefore, regular testing of fecal samples from suspected holdings and high turnover premises was fundamental to identifying virus circulation and to achieve SVD eradication. In this study, we evaluated diagnostic performances of six genomic amplification methods, using positive fecal samples from 78 different outbreaks (1997–2014), which included different lineages. Comparison of three RT-PCRs, designed to amplify the same 154 nt portion of the gene 3D, demonstrated that a conventional and a real-time based on SYBR Green detection assay showed the highest diagnostic sensitivity, detecting all samples, while a real-time TaqMan-based test missed three cases, owing to two mismatches in the probe target sequence. Diagnostic and analytical specificities were optimal, as 300 negative field samples and other enteroviruses reacted negative. Three further evaluated tests, previously described, were a 3D-targeted reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) and two real-time RT-PCRs targeted on the 5′UTR region. Here, the presence of multiple mismatches in probe and primers reduced the diagnostic performances, and two of the assays were unable to detect viruses from one sub-lineage. These results highlight that the choice of tests using less nucleotide targets significantly contributed to the success of the SVD eradication plan. Full article
(This article belongs to the Section Animal Viruses)
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Open AccessArticle
Neurological Findings in Children without Congenital Microcephaly Exposed to Zika Virus in Utero: A Case Series Study
Viruses 2020, 12(11), 1335; https://doi.org/10.3390/v12111335 - 20 Nov 2020
Viewed by 247
Abstract
The Zika virus can induce a disruptive sequence in the fetal brain and is manifested mainly by microcephaly. Knowledge gaps still exist as to whether the virus can cause minor disorders that are perceived later on during the first years of life in [...] Read more.
The Zika virus can induce a disruptive sequence in the fetal brain and is manifested mainly by microcephaly. Knowledge gaps still exist as to whether the virus can cause minor disorders that are perceived later on during the first years of life in children who are exposed but are asymptomatic at birth. In this case series, we describe the outcomes related to neurodevelopment through the neurological assessment of 26 non-microcephalic children who had intrauterine exposure to Zika virus. Children were submitted for neurological examinations and Bayley Scales-III (cognition, language, and motor performance). The majority (65.4%) obtained satisfactory performance in neurodevelopment. The most impaired domain was language, with 30.7% impairment. Severe neurological disorders occurred in five children (19.2%) and these were spastic hemiparesis, epilepsy associated with congenital macrocephaly (Zika and human immunodeficiency virus), two cases of autism (one exposed to Zika and Toxoplasma gondii) and progressive sensorineural hearing loss (GJB2 mutation). We concluded that non-microcephalic children with intrauterine exposure to Zika virus, in their majority, had achieved satisfactory performance in all neurodevelopmental domains. One third of the cases had some impairment, but the predominant group had mild alterations, with low occurrence of moderate to severe disorders, similar to other studies in Brazil. Full article
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Open AccessReview
Interplay between Hepatitis D Virus and the Interferon Response
Viruses 2020, 12(11), 1334; https://doi.org/10.3390/v12111334 - 20 Nov 2020
Viewed by 317
Abstract
Chronic hepatitis D (CHD) is the most severe form of viral hepatitis, with rapid progression of liver-related diseases and high rates of development of hepatocellular carcinoma. The causative agent, hepatitis D virus (HDV), contains a small (approximately 1.7 kb) highly self-pairing single-strand circular [...] Read more.
Chronic hepatitis D (CHD) is the most severe form of viral hepatitis, with rapid progression of liver-related diseases and high rates of development of hepatocellular carcinoma. The causative agent, hepatitis D virus (HDV), contains a small (approximately 1.7 kb) highly self-pairing single-strand circular RNA genome that assembles with the HDV antigen to form a ribonucleoprotein (RNP) complex. HDV depends on hepatitis B virus (HBV) envelope proteins for envelopment and de novo hepatocyte entry; however, its intracellular RNA replication is autonomous. In addition, HDV can amplify HBV independently through cell division. Cellular innate immune responses, mainly interferon (IFN) response, are crucial for controlling invading viruses, while viruses counteract these responses to favor their propagation. In contrast to HBV, HDV activates profound IFN response through the melanoma differentiation antigen 5 (MDA5) pathway. This cellular response efficiently suppresses cell-division-mediated HDV spread and, to some extent, early stages of HDV de novo infection, but only marginally impairs RNA replication in resting hepatocytes. In this review, we summarize the current knowledge on HDV structure, replication, and persistence and subsequently focus on the interplay between HDV and IFN response, including IFN activation, sensing, antiviral effects, and viral countermeasures. Finally, we discuss crosstalk with HBV. Full article
(This article belongs to the Special Issue Innate Immune Sensing of Viruses and Viral Evasion)
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Open AccessCommunication
Population Difference in Allele Frequency of HLA-C*05 and Its Correlation with COVID-19 Mortality
Viruses 2020, 12(11), 1333; https://doi.org/10.3390/v12111333 - 20 Nov 2020
Viewed by 308
Abstract
Background: coronavirus disease 2019 (COVID-19) causes severe illness including cytokine storms, but mortality among countries differs largely. In the present study, we investigated the association between human leukocyte antigen (HLA) class I, which plays a major role in susceptibility to viral infections, and [...] Read more.
Background: coronavirus disease 2019 (COVID-19) causes severe illness including cytokine storms, but mortality among countries differs largely. In the present study, we investigated the association between human leukocyte antigen (HLA) class I, which plays a major role in susceptibility to viral infections, and the mortality of COVID-19. Methods: data of allele frequencies of HLA-A, -B and -C and COVID-19 mortality were obtained for 74 countries from the Allele Frequency Net Database and worldometer.info. Association between allele frequency of each HLA and mortality was assessed by linear regression followed by multivariable regression. Subsequently, association of HLA-C*05 to its receptor KIR2DS4fl, expressed on natural killer (NK) cells, and differential mortality to historic pandemics were analyzed. Results: HLA-A*01, -B*07, -B*08, -B*44 and -C*05 were significantly associated with the risk of deaths (adjusted p = 0.040, 0.00081, 0.047, 0.0022, 0.00032, respectively), but only HLA-C*05 remained statistically significant (p = 0.000027) after multivariable regression. A 1% increase in the allele frequency of HLA-C*05 was associated with an increase of 44 deaths/million. Countries with different mortality could be categorized by the distribution of HLA-C*05 and its receptor KIR2DS4fl, which in combination cause NK cell-induced hyperactive immune response. Countries with similar ethnic and/or geographic background responded in a similar pattern to each pandemic. Conclusions: we demonstrated that allele frequency of HLA-C*05 and the distribution pattern with its receptor KIR2DS4fl strongly correlated with COVID-19 mortality. Host genetic variance of innate immunity may contribute to the difference in mortality among various countries and further investigation using patient samples is warranted. Full article
(This article belongs to the Special Issue Virus-Induced Cytokine Storms)
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Open AccessArticle
Virome Variation during Sea Star Wasting Disease Progression in Pisaster ochraceus (Asteroidea, Echinodermata)
Viruses 2020, 12(11), 1332; https://doi.org/10.3390/v12111332 - 20 Nov 2020
Viewed by 429
Abstract
Sea star wasting disease (SSWD) is a condition that has affected asteroids for over 120 years, yet mechanistic understanding of this wasting etiology remains elusive. We investigated temporal virome variation in two Pisaster ochraceus specimens that wasted in the absence of external stimuli [...] Read more.
Sea star wasting disease (SSWD) is a condition that has affected asteroids for over 120 years, yet mechanistic understanding of this wasting etiology remains elusive. We investigated temporal virome variation in two Pisaster ochraceus specimens that wasted in the absence of external stimuli and two specimens that did not experience SSWD for the duration of our study, and compared viromes of wasting lesion margin tissues to both artificial scar margins and grossly normal tissues over time. Global assembly of all SSWD-affected tissue libraries resulted in 24 viral genome fragments represented in >1 library. Genome fragments mostly matched densoviruses and picornaviruses with fewer matching nodaviruses, and a sobemovirus. Picornavirus-like and densovirus-like genome fragments were most similar to viral genomes recovered in metagenomic study of other marine invertebrates. Read recruitment revealed only two picornavirus-like genome fragments that recruited from only SSWD-affected specimens, but neither was unique to wasting lesions. Wasting lesion margin reads recruited to a greater number of viral genotypes (i.e., richness) than did either scar tissue and grossly normal tissue reads. Taken together, these data suggest that no single viral genome fragment was associated with SSWD. Rather, wasting lesion margins may generally support viral proliferation. Full article
(This article belongs to the Special Issue Viruses of Aquatic Ecosystems)
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Open AccessArticle
Fatal Interstitial Pneumonia Associated with Bovine Coronavirus in Cows from Southern Italy
Viruses 2020, 12(11), 1331; https://doi.org/10.3390/v12111331 - 19 Nov 2020
Viewed by 340
Abstract
An outbreak of winter dysentery, complicated by severe respiratory syndrome, occurred in January 2020 in a high production dairy cow herd located in a hilly area of the Calabria region. Of the 52 animals belonging to the farm, 5 (9.6%) died with severe [...] Read more.
An outbreak of winter dysentery, complicated by severe respiratory syndrome, occurred in January 2020 in a high production dairy cow herd located in a hilly area of the Calabria region. Of the 52 animals belonging to the farm, 5 (9.6%) died with severe respiratory distress, death occurring 3–4 days after the appearance of the respiratory signs (caught and gasping breath). Microbiological analysis revealed absence of pathogenic bacteria whilst Real-time PCR identified the presence of RNA from Bovine Coronavirus (BCoV) in several organs: lungs, small intestine (jejunum), mediastinal lymph nodes, liver and placenta. BCoV was therefore hypothesized to play a role in the lethal pulmonary infection. Like the other CoVs, BCoV is able to cause different syndromes. Its role in calf diarrhea and in mild respiratory disease is well known: we report instead the involvement of this virus in a severe and fatal respiratory disorder, with symptoms and disease evolution resembling those of Severe Acute Respiratory Syndromes (SARS). Full article
(This article belongs to the Special Issue Enteric Viruses in Animals)
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Open AccessBrief Report
Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation
Viruses 2020, 12(11), 1330; https://doi.org/10.3390/v12111330 - 19 Nov 2020
Viewed by 279
Abstract
With the current widespread use of dolutegravir in low-income countries, the understanding of the impact of nucleoside reverse transcriptase inhibitor (NRTI-) associated mutations on the efficacy of dolutegravir-containing antiretroviral therapy (ART) is of utmost importance. We describe a rare case of a patient [...] Read more.
With the current widespread use of dolutegravir in low-income countries, the understanding of the impact of nucleoside reverse transcriptase inhibitor (NRTI-) associated mutations on the efficacy of dolutegravir-containing antiretroviral therapy (ART) is of utmost importance. We describe a rare case of a patient with pre-existing M184V/I mutation and virological failure on a dolutegravir/lamivudine/abacavir regimen with the emergence of integrase strand transfer inhibitor resistance mutations. Additional risk factors, which may have triggered the virological failure, included suboptimal adherence and low nadir CD4+ cell count. This case illustrates that dolutegravir-containing triple-therapy should be prescribed with caution to patients with pre-existing M184V/I mutation and poor efficacy of the reverse transcriptase inhibitor backbone. In addition, this case highlights the need for viral load monitoring in patients on dolutegravir-containing regimens in settings with a high prevalence of the M184V/I mutation such as in low-income countries. Full article
(This article belongs to the Section Antivirals & Vaccines)
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Open AccessArticle
Serpentovirus (Nidovirus) and Orthoreovirus Coinfection in Captive Veiled Chameleons (Chamaeleo calyptratus) with Respiratory Disease
Viruses 2020, 12(11), 1329; https://doi.org/10.3390/v12111329 - 19 Nov 2020
Viewed by 859
Abstract
Serpentoviruses are an emerging group of nidoviruses known to cause respiratory disease in snakes and have been associated with disease in other non-avian reptile species (lizards and turtles). This study describes multiple episodes of respiratory disease-associated mortalities in a collection of juvenile veiled [...] Read more.
Serpentoviruses are an emerging group of nidoviruses known to cause respiratory disease in snakes and have been associated with disease in other non-avian reptile species (lizards and turtles). This study describes multiple episodes of respiratory disease-associated mortalities in a collection of juvenile veiled chameleons (Chamaeleo calyptratus). Histopathologic lesions included rhinitis and interstitial pneumonia with epithelial proliferation and abundant mucus. Metagenomic sequencing detected coinfection with two novel serpentoviruses and a novel orthoreovirus. Veiled chameleon serpentoviruses are most closely related to serpentoviruses identified in snakes, lizards, and turtles (approximately 40–50% nucleotide and amino acid identity of ORF1b). Veiled chameleon orthoreovirus is most closely related to reptilian orthoreoviruses identified in snakes (approximately 80–90% nucleotide and amino acid identity of the RNA-dependent RNA polymerase). A high prevalence of serpentovirus infection (>80%) was found in clinically healthy subadult and adult veiled chameleons, suggesting the potential for chronic subclinical carriers. Juvenile veiled chameleons typically exhibited a more rapid progression compared to subadults and adults, indicating a possible age association with morbidity and mortality. This is the first description of a serpentovirus infection in any chameleon species. A causal relationship between serpentovirus infection and respiratory disease in chameleons is suspected. The significance of orthoreovirus coinfection remains unknown. Full article
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Open AccessReview
Rhinovirus-Induced Modulation of Epithelial Phenotype: Role in Asthma
Viruses 2020, 12(11), 1328; https://doi.org/10.3390/v12111328 - 19 Nov 2020
Viewed by 264
Abstract
Human rhinoviruses have been linked both to the susceptibility of asthma development and to the triggering of acute exacerbations. Given that the human airway epithelial cell is the primary site of human rhinovirus (HRV) infection and replication, the current review focuses on how [...] Read more.
Human rhinoviruses have been linked both to the susceptibility of asthma development and to the triggering of acute exacerbations. Given that the human airway epithelial cell is the primary site of human rhinovirus (HRV) infection and replication, the current review focuses on how HRV-induced modulation of several aspects of epithelial cell phenotype could contribute to the development of asthma or to the induction of exacerbations. Modification of epithelial proinflammatory and antiviral responses are considered, as are alterations in an epithelial barrier function and cell phenotype. The contributions of the epithelium to airway remodeling and to the potential modulation of immune responses are also considered. The potential interactions of each type of HRV-induced epithelial phenotypic changes with allergic sensitization and allergic phenotype are also considered in the context of asthma development and of acute exacerbations. Full article
(This article belongs to the Special Issue Rhinovirus Infections)
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Open AccessReview
Achievements and Challenges of Classical Swine Fever Eradication in Brazil
Viruses 2020, 12(11), 1327; https://doi.org/10.3390/v12111327 - 19 Nov 2020
Viewed by 389
Abstract
Classical swine fever virus (CSFV) causes one of the most critical diseases in the porcine industry worldwide. In Brazil, the first description of the infection was reported in 1888, and the national recognition of the first free zone (FZ) occurred in 2001. Brazil [...] Read more.
Classical swine fever virus (CSFV) causes one of the most critical diseases in the porcine industry worldwide. In Brazil, the first description of the infection was reported in 1888, and the national recognition of the first free zone (FZ) occurred in 2001. Brazil has been recently recognized (2015–2016) by the World Organisation for Animal Health (OIE) with an FZ involving 15 states and the Federal District, corresponding to 95% of the industrial production of pigs in the country, and a non-free zone (NFZ), comprised by the North and Northeast regions of the country, with approximately 18% of the national pig herd and 5% of industrial production. This review aims to describe the history, the control and eradication actions, the recent occurrence of outbreaks in the NFZ, and the results obtained by the surveillance systems’ action in the FZ for CSF in Brazil since its creation. In the passive surveillance system, the notification of the suspect cases of classical swine fever (CSF) is mandatory while in the active surveillance system adopted in the FZ consists of serological monitoring of certified swine breeding farms (CSBFs), intensive pig farming (IPF), non-technified pig herds (NTPig), surveillance in slaughterhouses and monitoring the populations of wild pigs. In this region, the last outbreaks of the disease occurred in 1998, while in the NFZ, 28 outbreaks were detected from 2005 to 2017, with an apparent lethality rate of 93.96% (840/894). However, in 2018 and 2019, 68 new outbreaks were registered with an apparent lethality rate of 75.05% (1095/1459). Therefore, in 2019, the Brazil CSF-Free Strategic Plan was created to eradicate the infection from the country’s NFZ, since outbreaks in this region present a risk of reintroducing the disease FZ. Finally, differences in characteristics between the regions show factors that still need to be considered for the construction of a robust surveillance system in the NFZ and some improvements in the FZ. Thus, the control of CSF throughout the Brazilian territory requires strict sanitary guidelines, promoting animal health and, consequently, the national production chain’s competitiveness. Full article
(This article belongs to the Special Issue Endemic and Emerging Swine Viruses)
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Open AccessArticle
The Structure of an AAV5-AAVR Complex at 2.5 Å Resolution: Implications for Cellular Entry and Immune Neutralization of AAV Gene Therapy Vectors
Viruses 2020, 12(11), 1326; https://doi.org/10.3390/v12111326 - 18 Nov 2020
Viewed by 437
Abstract
Adeno-Associated Virus is the leading vector for gene therapy. Although it is the vector for all in vivo gene therapies approved for clinical use by the US Food and Drug Administration, its biology is still not yet fully understood. It has been shown [...] Read more.
Adeno-Associated Virus is the leading vector for gene therapy. Although it is the vector for all in vivo gene therapies approved for clinical use by the US Food and Drug Administration, its biology is still not yet fully understood. It has been shown that different serotypes of AAV bind to their cellular receptor, AAVR, in different ways. Previously we have reported a 2.4Å structure of AAV2 bound to AAVR that shows ordered structure for only one of the two AAVR domains with which AAV2 interacts. In this study we present a 2.5Å resolution structure of AAV5 bound to AAVR. AAV5 binds to the first polycystic kidney disease (PKD) domain of AAVR that was not ordered in the AAV2 structure. Interactions of AAV5 with AAVR are analyzed in detail, and the implications for AAV2 binding are explored through molecular modeling. Moreover, we find that binding sites for the antibodies ADK5a, ADK5b, and 3C5 on AAV5 overlap with the binding site of AAVR. These insights provide a structural foundation for development of gene therapy agents to better evade immune neutralization without disrupting cellular entry. Full article
(This article belongs to the Special Issue In Memory of Michael Rossmann)
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Open AccessArticle
Target-Centered Drug Repurposing Predictions of Human Angiotensin-Converting Enzyme 2 (ACE2) and Transmembrane Protease Serine Subtype 2 (TMPRSS2) Interacting Approved Drugs for Coronavirus Disease 2019 (COVID-19) Treatment through a Drug-Target Interaction Deep Learning Model
Viruses 2020, 12(11), 1325; https://doi.org/10.3390/v12111325 - 18 Nov 2020
Viewed by 449
Abstract
Previously, our group predicted commercially available Food and Drug Administration (FDA) approved drugs that can inhibit each step of the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using a deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI). Unfortunately, [...] Read more.
Previously, our group predicted commercially available Food and Drug Administration (FDA) approved drugs that can inhibit each step of the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using a deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI). Unfortunately, additional clinically significant treatment options since the approval of remdesivir are scarce. To overcome the current coronavirus disease 2019 (COVID-19) more efficiently, a treatment strategy that controls not only SARS-CoV-2 replication but also the host entry step should be considered. In this study, we used MT-DTI to predict FDA approved drugs that may have strong affinities for the angiotensin-converting enzyme 2 (ACE2) receptor and the transmembrane protease serine 2 (TMPRSS2) which are essential for viral entry to the host cell. Of the 460 drugs with Kd of less than 100 nM for the ACE2 receptor, 17 drugs overlapped with drugs that inhibit the interaction of ACE2 and SARS-CoV-2 spike reported in the NCATS OpenData portal. Among them, enalaprilat, an ACE inhibitor, showed a Kd value of 1.5 nM against the ACE2. Furthermore, three of the top 30 drugs with strong affinity prediction for the TMPRSS2 are anti-hepatitis C virus (HCV) drugs, including ombitasvir, daclatasvir, and paritaprevir. Notably, of the top 30 drugs, AT1R blocker eprosartan and neuropsychiatric drug lisuride showed similar gene expression profiles to potential TMPRSS2 inhibitors. Collectively, we suggest that drugs predicted to have strong inhibitory potencies to ACE2 and TMPRSS2 through the DTI model should be considered as potential drug repurposing candidates for COVID-19. Full article
(This article belongs to the Special Issue Drug-Repositioning Opportunities for Antiviral Therapy)
Open AccessReview
Application of Viral Vectors for Vaccine Development with a Special Emphasis on COVID-19
Viruses 2020, 12(11), 1324; https://doi.org/10.3390/v12111324 - 18 Nov 2020
Viewed by 460
Abstract
Viral vectors can generate high levels of recombinant protein expression providing the basis for modern vaccine development. A large number of different viral vector expression systems have been utilized for targeting viral surface proteins and tumor-associated antigens. Immunization studies in preclinical animal models [...] Read more.
Viral vectors can generate high levels of recombinant protein expression providing the basis for modern vaccine development. A large number of different viral vector expression systems have been utilized for targeting viral surface proteins and tumor-associated antigens. Immunization studies in preclinical animal models have evaluated the elicited humoral and cellular responses and the possible protection against challenges with lethal doses of infectious pathogens or tumor cells. Several vaccine candidates for both infectious diseases and various cancers have been subjected to a number of clinical trials. Human immunization trials have confirmed safe application of viral vectors, generation of neutralizing antibodies and protection against challenges with lethal doses. A special emphasis is placed on COVID-19 vaccines based on viral vectors. Likewise, the flexibility and advantages of applying viral particles, RNA replicons and DNA replicon vectors of self-replicating RNA viruses for vaccine development are presented. Full article
(This article belongs to the Special Issue The Application of Viruses to Biotechnology)
Open AccessArticle
Characterization of Clinical and Carrier Streptococcus agalactiae and Prophage Contribution to the Strain Variability
Viruses 2020, 12(11), 1323; https://doi.org/10.3390/v12111323 - 18 Nov 2020
Viewed by 230
Abstract
Streptococcus agalactiae (group B Streptococcus, GBS) represents a leading cause of invasive bacterial infections in newborns and is also responsible for diseases in older and immunocompromised adults. Prophages represent an important factor contributing to the genome plasticity and evolution of new strains. In [...] Read more.
Streptococcus agalactiae (group B Streptococcus, GBS) represents a leading cause of invasive bacterial infections in newborns and is also responsible for diseases in older and immunocompromised adults. Prophages represent an important factor contributing to the genome plasticity and evolution of new strains. In the present study, prophage content was analyzed in human GBS isolates. Thirty-seven prophages were identified in genomes of 20 representative sequenced strains. On the basis of the sequence comparison, we divided the prophages into eight groups named A–H. This division also corresponded to the clustering of phage integrase, even though several different integration sites were observed in some relative prophages. Next, PCR method was used for detection of the prophages in 123 GBS strains from adult hospitalized patients and from pregnancy screening. At least one prophage was present in 105 isolates (85%). The highest prevalence was observed for prophage group A (71%) and satellite prophage group B (62%). Other groups were detected infrequently (1–6%). Prophage distribution did not differ between clinical and screening strains, but it was unevenly distributed in MLST (multi locus sequence typing) sequence types. High content of full-length and satellite prophages detected in present study implies that prophages could be beneficial for the host bacterium and could contribute to evolution of more adapted strains. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease)
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Open AccessReview
Role of CCCH-Type Zinc Finger Proteins in Human Adenovirus Infections
Viruses 2020, 12(11), 1322; https://doi.org/10.3390/v12111322 - 18 Nov 2020
Viewed by 303
Abstract
The zinc finger proteins make up a significant part of the proteome and perform a huge variety of functions in the cell. The CCCH-type zinc finger proteins have gained attention due to their unusual ability to interact with RNA and thereby control different [...] Read more.
The zinc finger proteins make up a significant part of the proteome and perform a huge variety of functions in the cell. The CCCH-type zinc finger proteins have gained attention due to their unusual ability to interact with RNA and thereby control different steps of RNA metabolism. Since virus infections interfere with RNA metabolism, dynamic changes in the CCCH-type zinc finger proteins and virus replication are expected to happen. In the present review, we will discuss how three CCCH-type zinc finger proteins, ZC3H11A, MKRN1, and U2AF1, interfere with human adenovirus replication. We will summarize the functions of these three cellular proteins and focus on their potential pro- or anti-viral activities during a lytic human adenovirus infection. Full article
(This article belongs to the Special Issue Adenovirus Pathogenesis)
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Open AccessArticle
Understanding Pediatric Norovirus Epidemiology: A Decade of Study among Ghanaian Children
Viruses 2020, 12(11), 1321; https://doi.org/10.3390/v12111321 - 18 Nov 2020
Viewed by 267
Abstract
Understanding the epidemiology of human norovirus infection in children within Ghana and the entire sub-Saharan African region, where future norovirus vaccines would have the greatest impact, is essential. We analyzed 1337 diarrheic stool samples collected from children <5 years from January 2008 to [...] Read more.
Understanding the epidemiology of human norovirus infection in children within Ghana and the entire sub-Saharan African region, where future norovirus vaccines would have the greatest impact, is essential. We analyzed 1337 diarrheic stool samples collected from children <5 years from January 2008 to December 2017 and found 485 (36.2%) shedding the virus. GII.4 (54.1%), GII.3 (7.7%), GII.6 (5.3%), GII.17 (4.7%), and GII.5 (4.7%) were the most common norovirus genotypes. Although norovirus GII.4 remained the predominant capsid genotype throughout the study period, an increase in GII.6 and GII.3 capsid genotypes was observed in 2013 and 2014, respectively. The severity of clinical illness in children infected with GII.4 norovirus strains was similar to illness caused by non-GII.4 strains. Since the epidemiology of norovirus changes rapidly, establishment of systematic surveillance within sentinel sites across the country would enhance the monitoring of circulating norovirus strains and allow continuous understanding of norovirus infection in Ghana. Full article
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Open AccessArticle
Transcriptional Landscape of Staphylococcus aureus Kayvirus Bacteriophage vB_SauM-515A1
Viruses 2020, 12(11), 1320; https://doi.org/10.3390/v12111320 - 17 Nov 2020
Viewed by 314
Abstract
The Twort-like myoviruses (Kayvirus genus) of S. aureus are promising agents for bacteriophage therapy due to a broad host range and high killing activity against clinical isolates. This work improves the current understanding of the phage infection physiology by transcriptome analysis. The [...] Read more.
The Twort-like myoviruses (Kayvirus genus) of S. aureus are promising agents for bacteriophage therapy due to a broad host range and high killing activity against clinical isolates. This work improves the current understanding of the phage infection physiology by transcriptome analysis. The expression profiles of a typical member of the Kayvirus genus (vB_SauM-515A1) were obtained at three time-points post-infection using RNA sequencing. A total of 35 transcription units comprising 238 ORFs were established. The sequences for 58 early and 12 late promoters were identified in the phage genome. The early promoters represent the strong sigma-70 promoters consensus sequence and control the host-dependent expression of 26 transcription units (81% of genes). The late promoters exclusively controlled the expression of four transcription units, while the transcription of the other five units was directed by both types of promoters. The characteristic features of late promoters were long -10 box of TGTTATATTA consensus sequence and the absence of -35 boxes. The data obtained are also of general interest, demonstrating a strategy of the phage genome expression with a broad overlap of the early and late transcription phases without any middle transcription, which is unusual for the large phage genomes (>100 kbp). Full article
(This article belongs to the Special Issue Viruses of Microbes 2020: The Latest Conquests on Viruses of Microbes)
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Open AccessArticle
A Novel Sub-Lineage of Chikungunya Virus East/Central/South African Genotype Indian Ocean Lineage Caused Sequential Outbreaks in Bangladesh and Thailand
Viruses 2020, 12(11), 1319; https://doi.org/10.3390/v12111319 - 17 Nov 2020
Viewed by 448
Abstract
In recent decades, chikungunya virus (CHIKV) has become geographically widespread. In 2004, the CHIKV East/Central/South African (ECSA) genotype moved from Africa to Indian ocean islands and India followed by a large epidemic in Southeast Asia. In 2013, the CHIKV Asian genotype drove an [...] Read more.
In recent decades, chikungunya virus (CHIKV) has become geographically widespread. In 2004, the CHIKV East/Central/South African (ECSA) genotype moved from Africa to Indian ocean islands and India followed by a large epidemic in Southeast Asia. In 2013, the CHIKV Asian genotype drove an outbreak in the Americas. Since 2016, CHIKV has re-emerged in the Indian subcontinent and Southeast Asia. In the present study, CHIKVs were obtained from Bangladesh in 2017 and Thailand in 2019, and their nearly full genomes were sequenced. Phylogenetic analysis revealed that the recent CHIKVs were of Indian Ocean Lineage (IOL) of genotype ECSA, similar to the previous outbreak. However, these CHIKVs were all clustered into a new distinct sub-lineage apart from the past IOL CHIKVs, and they lacked an alanine-to-valine substitution at position 226 of the E1 envelope glycoprotein, which enhances CHIKV replication in Aedes albopictus. Instead, all the re-emerged CHIKVs possessed mutations of lysine-to-glutamic acid at position 211 of E1 and valine-to-alanine at position 264 of E2. Molecular clock analysis suggested that the new sub-lineage CHIKV was introduced to Bangladesh around late 2015 and Thailand in early 2017. These results suggest that re-emerged CHIKVs have acquired different adaptations than the previous CHIKVs. Full article
(This article belongs to the Special Issue RNA Viruses: Structure, Adaptation, and Evolution)
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Open AccessReview
The Present Status of Immuno-Oncolytic Viruses in the Treatment of Pancreatic Cancer
Viruses 2020, 12(11), 1318; https://doi.org/10.3390/v12111318 - 17 Nov 2020
Viewed by 398
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the fifth leading cause of cancer-related death in Western countries. The incidence of PDAC has increased over the last 40 years and is projected to be the second leading cause of cancer death by 2030. Despite aggressive treatment [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is the fifth leading cause of cancer-related death in Western countries. The incidence of PDAC has increased over the last 40 years and is projected to be the second leading cause of cancer death by 2030. Despite aggressive treatment regimens, prognosis for patients diagnosed with PDAC is very poor; PDAC has the lowest 5-year survival rate for any form of cancer in the United States (US). PDAC is very rarely detected in early stages when surgical resection can be performed. Only 20% of cases are suitable for surgical resection; this remains the only curative treatment when combined with adjuvant chemotherapy. Treatment regimens excluding surgical intervention such as chemotherapeutic treatments are associated with adverse effects and genetherapy strategies also struggle with lack of specificity and/or efficacy. The lack of effective treatments for this disease highlights the necessity for innovation in treatment options for patients diagnosed with early- to late-phase PDAC and immuno-oncolytic viruses (OVs) have been of particular interest since 2006 when the first oncolytic virus was approved as a therapy for nasopharyngeal cancers in China. Interest resurged in 2015 when T-Vec, an oncolytic herpes simplex virus, was approved in the United States for treatment of advanced melanoma. While many vectors have been explored, few show promise as treatment for pancreatic cancer, and fewer still have progressed to clinical trial evaluation. This review outlines recent strategies in the development of OVs targeting treatment of PDAC, current state of preclinical and clinical investigation and application. Full article
(This article belongs to the Section Animal Viruses)
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Open AccessArticle
Marek’s Disease Virus Cluster 3 miRNAs Restrict Virus’ Early Cytolytic Replication and Pathogenesis
Viruses 2020, 12(11), 1317; https://doi.org/10.3390/v12111317 - 17 Nov 2020
Viewed by 247
Abstract
Herpesvirus-encoded microRNAs (miRNAs) have been discovered in infected cells; however, lack of a suitable animal model has hampered functional analyses of viral miRNAs in vivo. Marek’s disease virus (MDV) (Gallid alphaherpesvirus 2, GaHV-2) genome contains 14 miRNA precursors, which encode 26 mature [...] Read more.
Herpesvirus-encoded microRNAs (miRNAs) have been discovered in infected cells; however, lack of a suitable animal model has hampered functional analyses of viral miRNAs in vivo. Marek’s disease virus (MDV) (Gallid alphaherpesvirus 2, GaHV-2) genome contains 14 miRNA precursors, which encode 26 mature miRNAs, grouped into three clusters. In this study, the role of MDV-encoded cluster 3 miRNAs, also known as mdv1-miR-M8-M10, in pathogenesis was evaluated in chickens, the natural host of MDV. Our results show that deletion of cluster 3 miRNAs did not affect virus replication and plaque size in cell culture, but increased early cytolytic replication of MDV in chickens. We also observed that deletion of cluster 3 miRNAs resulted in significantly higher virus reactivation from peripheral blood lymphocytes. In addition, pathogenesis studies showed that deletion of cluster 3 miRNAs resulted in more severe atrophy of lymphoid organs and reduced mean death time, but did not affect the incidence of MDV-associated visceral tumors. We confirmed these results by generating a cluster 3 miRNA revertant virus in which the parental MDV phenotype was restored. To the best of our knowledge, our study provides the first evidence that MDV cluster 3 miRNAs play an important role in modulating MDV pathogenesis. Full article
(This article belongs to the Special Issue Animal Herpesviruses Pathogenesis and Immunity)
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Open AccessArticle
Wine Phenolic Compounds Differently Affect the Host-Killing Activity of Two Lytic Bacteriophages Infecting the Lactic Acid Bacterium Oenococcus oeni
Viruses 2020, 12(11), 1316; https://doi.org/10.3390/v12111316 - 17 Nov 2020
Viewed by 336
Abstract
To provide insights into phage-host interactions during winemaking, we assessed whether phenolic compounds modulate the phage predation of Oenococcus oeni. Centrifugal partition chromatography was used to fractionate the phenolic compounds of a model red wine. The ability of lytic oenophage OE33PA to [...] Read more.
To provide insights into phage-host interactions during winemaking, we assessed whether phenolic compounds modulate the phage predation of Oenococcus oeni. Centrifugal partition chromatography was used to fractionate the phenolic compounds of a model red wine. The ability of lytic oenophage OE33PA to kill its host was reduced in the presence of two collected fractions in which we identified five compounds. Three, namely, quercetin, myricetin and p-coumaric acid, significantly reduced the phage predation of O. oeni when provided as individual pure molecules, as also did other structurally related compounds such as cinnamic acid. Their presence was correlated with a reduced adsorption rate of phage OE33PA on its host. Strikingly, none of the identified compounds affected the killing activity of the distantly related lytic phage Vinitor162. OE33PA and Vinitor162 were shown to exhibit different entry mechanisms to penetrate into bacterial cells. We propose that ligand-receptor interactions that mediate phage adsorption to the cell surface are diverse in O. oeni and are subject to differential interference by phenolic compounds. Their presence did not induce any modifications in the cell surface as visualized by TEM. Interestingly, docking analyses suggest that quercetin and cinnamic acid may interact with the tail of OE33PA and compete with host recognition. Full article
(This article belongs to the Special Issue Viruses of Microbes 2020: The Latest Conquests on Viruses of Microbes)
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Open AccessReview
Viral Infections in Burn Patients: A State-Of-The-Art Review
Viruses 2020, 12(11), 1315; https://doi.org/10.3390/v12111315 - 17 Nov 2020
Viewed by 315
Abstract
Infections that are triggered by the accompanying immunosuppression in patients with burn wounds are very common regardless of age. Among burn patients, the most frequently diagnosed infections include the bacterial ones primarily caused by Pseudomonas aeruginosa or Klebsiella pneumonia, as well as [...] Read more.
Infections that are triggered by the accompanying immunosuppression in patients with burn wounds are very common regardless of age. Among burn patients, the most frequently diagnosed infections include the bacterial ones primarily caused by Pseudomonas aeruginosa or Klebsiella pneumonia, as well as fungal infections with the etiology of Candida spp. or Aspergillus spp. Besides, burn wounds are highly susceptible to viral infections mainly due to the impaired immune responses and defective functions of the immune cells within the wound microenvironment. The most prevalent viruses that invade burn wounds include herpes simplex virus (HSV), cytomegalovirus (CMV), human papilloma virus (HPV), and varicella zoster virus (VZV). Likewise, less prevalent infections such as those caused by the orf virus or Epstein–Barr Virus (EBV) might also occur in immunosuppressed burn patients. Viral infections result in increased morbidity and mortality rates in severely burned patients. Additionally, a positive correlation between the hospitalization duration and the severity of the viral infection has been demonstrated. Viral infections trigger the occurrence of various complications, ranging from mild symptoms to even fatal incidents. Accurate detection of viral infection is of great clinical importance because of the possibility for a quicker introduction of proper treatment therapy and shortening of hospitalization time. The aim of this paper is to provide a comprehensive review of the literature and summarize the findings regarding the most common viral infections in immunosuppressed burn patients. Full article
(This article belongs to the Section Animal Viruses)
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